early warning system

Charting the course towards an early warning system for chemicals

The PARC consortium has provided the vital building blocks for the development of a robust early warning system (EWS) for hazardous chemicals in a new report. 

The development of an EWS for hazardous chemicals is a pivotal element of PARC’s commitment to safeguarding public health and environmental quality. The EWS aims to proactively detect and assess potential risks caused by hazardous chemicals on a European level, serving as a rapid-response tool to enable mitigation actions and protect communities. In this effort, to identify chemical hazards, the detection of risks is intrinsically linked to the biological effects that these chemicals can cause. Consequently, to accurately estimate chemical risks, the inclusion of methods capable of identifying toxicity effects, known as effect-based methods, becomes indispensable.

New workflow identifies hazardous substances

Historically, the efficacy of effect-based methods was hindered by the time-consuming evaluation of chemical data, often requiring the identification of unknown chemicals through non-targeted chemical analysis, which could be laborious.

Recent strides in sample acquisition, preparation, and chemical analysis, have substantially reduced the required analytical timeframes, making effect-based methods more practical and efficient, and therefore enabling their use within early warning systems.

In a recent report, the PARC consortium has compiled advancements of effect-based methods and unveiled a state-of-the-art approach through an EWS workflow (Figure 1), which is designed to identify potentially hazardous substances, both new and existing. 

The building blocks described in the report

Within this approach, a series of critical components including effect-based methodologies come together to lay the groundwork for a comprehensive EWS. These vital building blocks for an EWS, that have been described in detail in the report, include:

  • Advanced Sampling Strategies: Techniques to secure representative samples from diverse environmental matrices
  • Optimized Sample Preparation Methods: Essential for conducting bioassays and chemical analyses with precision
  • Chemical Analytical Methods: Incorporating target, suspect, and non-target screening for accurate hazard identification
  • Effect-Based Monitoring (EBM): Leveraging bioassay-based monitoring techniques to identify biological and toxicological effects in environmental samples
  • Iceberg Modelling: A predictive tool that estimates effects based on known chemicals, which can form the "tip of the iceberg”
  • Effect-Directed Analysis (EDA): A comprehensive approach that goes beyond observing effects to identify the exact chemicals responsible for those effects

The suggested workflow

The workflow outlined in the figure , as detailed in the report, provides a structured approach to including effect-based methods in EWS. It is initiated through EBM, a process that utilises a wide array of bioassays - biological components capable of measuring responses to chemical exposure. These bioassays can serve as detectors of a spectrum of potential effects caused by chemicals. Based on this early screening, a preliminary early warning signal can be triggered, requiring confirmation through further investigation. The suggested workflow is outlined below:

  1. Effect-Based Monitoring (EBM): EBM involves the use of various bioassays to detect and assess the effects of chemicals. These bioassays can include cells or organisms that respond to chemical exposure, providing valuable insights into potential hazards.
  2. Effect-Based Trigger Values (EBTs): EBTs are predefined thresholds based on established data. They represent levels above which adverse effects are observed. When the results from EBM surpass these EBTs, it serves as an early indicator of potential harm to the environment or human health.
  3. Preliminary Early Warning Signal: If the data from EBM indicate that the effects exceed the EBTs, a preliminary early warning signal is triggered. This signal prompts further investigation to confirm the potential risk.
  4. Confirmation of Early Warning Signal: The confirmation process involves several steps:
    a.    Existing Toxicity Data: Initially, researchers may refer to existing toxicity data to assess the validity of the preliminary signal. This can include literature information on the effects of similar chemicals or substances.
    b.    Iceberg Modelling: If existing data does not confirm the signal or if additional insights are needed, iceberg modelling is employed. This modelling aims to determine if the observed effects can be explained by the presence of known chemicals. It relies on relative potency values for target analytes suspected of contributing to the observed effects in the bioassays.
    c.    Effect-Directed Analysis (EDA): If iceberg modelling cannot provide a satisfactory explanation for the observed effects or if it cannot be conducted, EDA is employed. EDA goes beyond mere observation of adverse effects and seeks to identify the specific chemicals responsible for these effects. It involves extract fractionation, bioassay-directed identification of bioactive fractions, chemical identification of bioactive chemicals, and confirmation of their toxicity.
  5. Confirmed Early Warning Signal: Upon successful confirmation of the toxicants and their adverse effects, a confirmed early warning signal is issued. This signal can trigger the appropriate risk management actions to mitigate potential harm and safeguard the environment or public health.


EWS workflow
Figure 1. The EWS workflow encompassing effect-based methods. Abbreviations: EBM (Effect-based Monitoring); EBT value (Effect-based Trigger value); EDA (Effect-directed Analysis).

More tools to be developed in PARC

The proposed approach, which leverages effect-based methods, serves as a cornerstone in developing a robust EWS that can be effectively used on an EU level; however, the development of an EWS within PARC represents a dynamic and multifaceted endeavour.

Several complementary tools and methodologies are currently being developed within PARC, poised to enhance the capabilities of the EWS further.

Innovative self-sampling approaches developed can expedite the detection of hazardous chemicals and enable timely responses.

Additionally, the development of new approach methodologies (NAMs) will be a step forward in chemical hazard assessment. These methodologies (e.g., in silico, in chemico, in vitro, and ex vivo approaches), which provide information on chemical hazards while avoiding the use of animals, are a more ethical and sustainable approach in chemical analysis and are expected to lead to further advancements in hazard identification.

The expansion of available databases, exemplified by the database being compiled on chemicals in products in PARC, is also expected to contribute to the effectiveness of the EWS.

Such innovative tools and methods are expected to bolster the EWS’s capacity to identify chemical hazards at an early stage, not only on a local but also on EU level, enabling PARC’s vision to become reality.

Read more in the report.